Nutritional status of infants at six months of age following maternal influenza immunization: A randomized placebo-controlled trial in rural Nepal.

BACKGROUND: Maternal influenza vaccination has increased birth weight in two randomized trials in South Asia but the impact on infant growth is unknown. METHODS: A randomized placebo-controlled trial of year round maternal influenza immunization was conducted in two annual cohorts in Sarlahi District, southern plains of Nepal, from April 2011 through April 2014. Infants born to women enrolled in the trial had weight, length, and head circumference measured at birth and 6 months of age. The study was powered for the 3 primary trial outcomes but not for stunting and wasting at 6 months of age. RESULTS: 3693 women received placebo or influenza vaccine between 17 and 34 weeks gestation, resulting in 3646 live births. About 72% of infants who survived had weight and length measurements between 150 and 210 days of age. Prevalence of stunting (<-2 Z scores length-for-age) was 14.8% in the placebo and 13.6% in the vaccine groups, respectively. Stunting < -3 Z scores was 3.2% versus 2.0% in placebo versus vaccine groups (RR: 0.64 (95% CI: 0.39, 1.04)). Wasting (< -2 Z scores weight for length) was 10.3% versus 11.0% for placebo versus vaccine groups. Severe wasting (< -3 Z scores weight for length) was 3.8% for placebo versus 2.6% for vaccine (RR: 0.69 (95% CI: 0.44, 1.07)). The impact of flu vaccine on wasting was greater in cohort 2 than in cohort 1, (RR: 0.66 (0.44, 0.99) for any wasting), and RR: 0.45 (0.19, 1.09) for severe wasting. This corresponded to a larger impact on birth weight and a better vaccine match with circulating viruses in cohort 2. CONCLUSIONS: Although maternal immunization reduced low birth weight by 15%, only wasting at 6 months in the 2nd cohort was statistically significantly difference. However, the study was underpowered to detect reductions of public health importance. TRIAL REGISTRATION: Clinicaltrials.gov (NCT01034254).